Research InterestsMy primary research interest involves the pathogenesis of obligate intracellular bacteria, including mechanisms of cell injury and cellular changes as seen by electron microscopy. Rocky Mountain spotted fever is a human disease caused by Rickettsia rickettsii. This microorganism, which is usually acquired by humans from the bite of a tick, initially invades the endothelial cells of capillaries where it replicates in the cytoplasm, and occasionally the nucleus, and rapidly destroys these cells. Subsequently, larger blood vessels may become involved. In severe cases of RMSF this cell destruction results in thrombosis and necrosis of these vessels. No known toxin is elaborated by this bacterium, yet only small numbers of these microorganisms are required to cause cell death. Previous morphological studies have shown that following infection by Rickettsia rickettsii, the rough-surfaced endoplasmic reticulum-outer nuclear envelope becomes severely distended, and biochemical studies have shown a concurrent increase in intracellular oxidant activity. These oxidants are most likely peroxides. Additionally, superoxide, another oxidant, is released at the cell surface during internalization of the rickettsiae, and the levels of several antioxidant enzymes which normally protect cells from oxidant injury, are significantly reduced. Current studies are designed to examine the role of oxygen radicals and oxidant stress on cellular injury caused by Rickettsia rickettsii using an human endothelial cell model, and to develop strategies to protect cells from injury by this microorganism.
Clifton, D.R., H. Huyck, E. Rydkina, G. Pryhuber, R.S. Freeman, D. J. Silverman, and S.K. Sahni. Rickettsia rickettsii Infection of Human Endothelial Cells Induces the Expression and Secretion of Chemokines IL-8 and MCP-1 Through the Activation of Nuclear Transcription Factor NF-kB. Internat?l J. Med. Microbiol. 295: 267-278 (2005).
Rydkina, E., D.J. Silverman, and S.K. Sahni. Activation of p38 Stress-Activated Protein Kinase during R. rickettsii Infection of Human Endothelial Cells: Role in the Induction of Chemokine Response. Cellular Microbiol. 7: 1519-1530 (2005).
Rydkina, E., D.J. Silverman, and S.K. Sahni., Similarities and Differences in Host Cell Signaling Following Infection with Different Rickettsia Species. Annals of the N.Y. Acad. Sci. 1063: 203-206 (2005).
Sahni, S.K., E. Rydkina, A. Sahni, S.G. Joshi, and D.J. Silverman., Potential Roles for Regulatory Oxygenases in Rickettsial Pathogenesis. Annals of the N.Y. Acad. Sci. 1063: 207-214 (2005).
Joshi, S.G., C.W. Francis, D.J. Silveman, and S.K. Sahni., NF-kB Activation Suppresses Host Cell Apoptosis during Rickettsia rickettsii Infection via Regulatory Effects on Intracellular Localization or Levels of Apoptogenic and Antiapoptotic Proteins. FEMS Microbiol. Letters 234: 333-341 (2004).
Rydkina, E., S.K. Sahni, L.A. Santucci, L.C. Turpin, R.B. Baggs, and D.J. Silverman., Selective Modulation of Antioxidant Enzyme Activities in Host Tissues during Rickettsia conorii Infection. Microb. Pathogen. 36: 293-301, 2004.
Eremeeva, M.E., G.A. Dasch, and D.J. Silverman., Evaluation of SQ-PCR, an Assay for Quantitation of Rickettsia rickettsii and Closely-Related Spotted Fever Group Rickettsiae. J. Clin. Microbiol. 41: 5466-5472 (2003).
Eremeeva, M.E., Klemt, R.M., L. A. Santucci-Domotor, D.J. Silverman, and G.A. Dasch , Genetic Analysis of Isolates of Rickettsia rickettsii which Differ in Virulence. Annals N.Y. Acad. Sci. 990 : 717-722 (2003).
Eremeeva, M.E., Z. Liang, C.Paddock, S. Zaki, J.G. Vandenbergh, G.A. Dasch, and D.J. Silverman. Rickettsia rickettsii Infection of the Pine Vole, Microtus pinetorum: Kinetics of Infection and Quantitation of Antioxidant Enzyme Gene Expression by RT-PCR. Annals N.Y. Acad. Sci. 990: 468-473 (2003).
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